Flavonoids, one of the oldest group of natural products, they shows various bioactivities, such as radio-protective, (Goel, H. C., Kumar, I. P., Samanta, N., Rana, S. V. S. Mol Cell Biochem. 2003, 245, 57-67), kinase inhibitory (Ya-ming, X., Jeffrey, A., Smith, J. A., Deborah, A., Lannigan, D. A., Sidney, M., Hecht, S. M. Bioorg. Med. Chem. 2006, 14, 3974-3977) and apoptotic activities related to cancer (Brusselmans, K., Vrolix, R., Verhoeven, G., Swinnen, J. V. J. Biol. Chem. 2005, 280, 5636-5645). They show antioxygenic and metal chelating activities (Gao, X. In Seabuckthorn, Hippophae L. Biochemistry and Pharmacology.; Singh, Virendra, Ed., Daya Publishing House: Delhi, 2006; Vol. II, pp 390-401), and have also been implicated in the conditions related to degenerative diseases (aging), wound healing and cardio-vascular problems. Recently exploiting flavonoids as candidates for prevention and treatment of osteoporosis have been gaining importance. Flavanoids having O-glycoside moiety show lot of interesting biological activities. For example rutin (quercetin-3-O-glucose rhamnose) inhibits the ovariectomy-induced resorption of bone in rats (Horcajada-Molteni, M.-N., Crespy, V., Coxam, V., Davicco, M.-J., Remesy, C., Barlet, J.-P. J. Bone Miner. Res. 2000, 15, 2251-2258). Quercetin which is a aglycon of rutin has been reported to inhibit the osteoclastic resorption of bone in vitro (Wattel, A., Kamel, S., Mentaverri, R., Lorget, F., Prouillet, C. Petit, J.-P., Fardelonne, P., Brazier, M. Biochem. Pharmacol. 2003, 65, 35-42; Notoya, M., Tsukamoto, Y., Nishimura, H., Woo, J.-T., Nagai, K., Lee, I.-S., Hagiwara, H. Eur. J. Pharmacol. 2004, 485, 89-96). But these 0-glycosides susceptible to undergo cleavage of glycosyl bond to give glycon and aglycon moieties in the biological system, therefore their stability in the biological system is questionable. Recently Rakesh mourya et. al isolated and identified three new C-glycosylated flavonoids considered as stable glycosides in the biological system namely (2S,3S)-(+)-3′,4′,5,7-tetrahydroxydihydroflavonol-6-C-β-D-glucopyranoside, (2S,3S)-(+)-4′,5,7-trihydroxy dihydro flavonol-6-C-β-D-glucopyranoside and 3-C-β-D-glucopyranoside-2,4,6-trihydroxymethylbenzoate from ulmus wallichiana plant (Rawat, Preeti; Kumar, Manmeet, Sharan, Kunal; Chattopadhyay, Naibedya; Maurya, Rakesh. Bioorg. Med. Chem. Lett. 2009, 19, 4684-4687) (WO 2009110003 A1). Which is known in traditional Indian medicinal practice to treat the bone fracture and assessed their activity in stimulating osteoblast differentiation. Stimulating of osteoblast differentiation is a bone anabolic function that is desirable for osteoporosis therapy. (2S,3S)-Taxifolin-6-C-β-D-glucopyranoside also known as ulmoside A or K058 is showing excellent bone deflecting activity.
(2R,3R)-Taxifolin-6-C-β-D-glucopyanoside is a natural product isolated from the medicinal plant Garcinia epunctata and a tree from Garcinia buchananii bark. This compound shows extraordinarily high antioxidative power {(Stark, T.; Matsutomo, T.; Losch, S.; Boakye, P.; Balemba, O.; pasilis, S.; Hofmann, T. J. Agric. Food Chem. 2012, 60, 2053-2062); (Mbafor, J. T.; Fomum, Z. T.; Promsattha, B.; Sanson, D. R.; Tempesta, M. S. J. Nat. Prod. 1989, 52, 417-419)}.
The above two compounds can only be obtained from the natural source in very small quantities. More over evaluation of their biological activity to develop into the drug requires more quantities of compound, for this a simple short and scalable strategy is indeed essential.
So far there are no reports on the synthesis of these compounds in the literature. Although there are some reports on the synthesis of flavone 6-C-β-D-gluco compounds (Carbohydrate Research. 2010, 345, 1825-1830) (WO 2011064726 A1) but so far there is no report of the synthesis of title compounds 1 and 2. Herein we are presenting the first total synthesis involving highly regioselective glycosidation of (−)-taxifolin and (+)-taxifolin to give the compounds ulmoside A (1) and (2R,3R) taxifolin6-C-β-D-glucopyranoside (2).
Structures of Some Flavonoids and O- and C-Glycosides of Flavonoids:
